The present invention relates generally to antibodies directed against Sialyl-Lewisa (sLea), and more specifically to polynucleotides encoding anti-sLea antibodies and the corresponding encoded antibodies or fragments thereof.
Passive administration of antibodies directed against tumor specific antigens may eliminate tumor cells and early metastases during cancer development. This treatment may also have a significant impact on cancer recurrence. Antibodies directed against tumor specific carbohydrates may be useful candidates in this cancer treatment. For example, many tumor-restricted monoclonal antibodies resulting from immunization of mice with human cancer cells have been shown to be directed against carbohydrate antigens expressed at the cell surface as glycolipids or glycoproteins. The carbohydrate sLea has been shown to be expressed on tumors of the gastrointestinal tract. Expression of sLea has also been shown to impact metastatic potential and correlates with increased metastatic potential in human colon cancer and pancreatic adenocarcinoma. However, carbohydrate chemistry has been rather challenging and the clinical development of antibodies that recognize such tumor specific carbohydrates has been slow.
Pancreatic carcinoma is one of the most aggressive adenocarcinomas and is often associated with a poor prognosis. Pancreatic carcinoma ranks as the fourth leading cause of cancer mortality. Despite advances in the screening for different carcinomas, the reliability of detecting malignant lesions stemming from the pancreas remains poor. Positron emission tomography utilizing fluorodeoxyglucase (FDG-PET) has been indicated for the detection and staging of pancreatic cancer. However, FDG-PET is insensitive to differentiating pancreatitis from malignancy and remains problematic in staging small primary lesions (<7 mm) and liver metastases (<1 cm). One diagnostic screening method used to monitor the state of pancreatic ductal adenocarcinoma (PDAC) patients includes detecting elevated levels of circulating sLea antigen in sera. Patients with >37 U/ml of circulating sLea antigen indicates cancer recurrence. However, development of alternative diagnostic tools that utilize such tumor specific carbohydrates has been slow.
Thus, there exists a need for identifying and generating antibodies that specifically recognize tumor specific carbohydrates, such as sLea, for the treatment of recurring cancers and for detecting malignant lesions and metastases. This invention satisfies this need and provides related advantages.